Combinatorial regulation of the dev operon by MrpC2 and FruA during Myxococcus xanthus development.

Proper expression of the dev operon is important for normal development of Myxococcus xanthus. When starved, these bacteria coordinate their gliding movements to build mounds that become fruiting bodies as some cells differentiate into spores. Mutations in the devTRS genes impair sporulation. Expression of the operon occurs within nascent fruiting bodies and depends in part on C signaling. Here, we report that expression of the dev operon, like that of several other C-signal-dependent genes, is subject to combinatorial control by the transcription factors MrpC2 and FruA. A DNA fragment upstream of the dev promoter was bound by a protein in an extract containing MrpC2, protecting the region spanning positions -77 to -54. Mutations in this region impaired binding of purified MrpC2 and abolished developmental expression of reporter fusions. The association of MrpC2 and/or its longer form, MrpC, with the dev promoter region depended on FruA in vivo, based on chromatin immunoprecipitation analysis, and purified FruA appeared to bind cooperatively with MrpC2 to DNA just upstream of the dev promoter in vitro. We conclude that cooperative binding of the two proteins to this promoter-proximal site is crucial for dev expression. 5' deletion analysis implied a second upstream positive regulatory site, which corresponded to a site of weak cooperative binding of MrpC2 and FruA and boosted dev expression 24 h into development. This site is unique among the C-signal-dependent genes studied so far. Deletion of this site in the M. xanthus chromosome did not impair sporulation under laboratory conditions.

New or unusual dermatopathology tumors: a review.

As experience is acquired, there is a constant evolution in both terminology and understanding of various relatively newly described tumors in the realm of dermatopathology. Several mesenchymal tumors of the lower extremity have undergone various changes in nomenclature, molecular discoveries, and histologic grading. Examples include hemosiderotic fibrohistiocytic lipomatous lesion/pleomorphic hyalinizing angiectatic tumor; superficial acral fibromyxoma; and myxoinflammatory fibroblastic sarcoma. Primary cutaneous myoepithelioma is also a relatively newly described entity for which grading and classification continue to evolve. Finally, even our understanding of the classic granular cell tumor has expanded to include a non-neural variant. This article reviews the current nomenclature, emerging concepts, and differential diagnosis of these evolving entities.

"The more you did, the more it made sense": Problem-based learning to improve early evidence-based practice in an undergraduate physiotherapy professional programme.

BACKGROUND AND PURPOSE: Evidence-based practice (EBP), which integrates clinical reasoning skills, research evidence, and patient preference, has become standard in curricula for health care professional programs. Students however perceive EBP as difficult and often irrelevant to clinical practice. METHODS: A problem-based learning (PBL) approach is trialled in an early stage module where EBP knowledge and skills are stated learning outcomes. Prior to this, the content-based approach to EBP teaching and learning received negative student feedback. The impact of delivering EBP through PBL is evaluated by comparing 5 standard Likert feedback scales and open-ended question responses relating to the EBP instruction in the module before and after a PBL approach was implemented. The impact of a PBL approach on EBP profiles is further examined under domains (relevance, sympathy, terminology, practice, and confidence) of the validated Evidence-based Practice Profile Questionnaire. RESULTS: All mean Likert scores relating to subject understanding, relevance of assessments, achievement of learning outcomes, teaching, and overall module satisfaction improved when the PBL approach was compared with the lecture-based format (p < 0.05). Student comment post-PBL continued to identify EBP as a difficult concept, but now comments on the teaching and assessment approach were mainly positive, addressing the collaborative nature of PBL, identifying EBP, communication and team-working skills acquired, praising the real life, practical application of EBP taken, and commenting on improvement in EBP self-efficacy. Within group change in the Evidence-based Practice Profile Questionnaire following a PBL approach identified significant improvement in EBP domains of terminology (mean change 3.38; p < 0.001); practice (mean change 16.5; p < 0.001), and confidence (mean change 10.1; p = 0.008). Conceptual links, based on constructivist underpinnings of PBL and EBP, are developed in the paper. CONCLUSIONS: Using mixed methods evaluation, PBL is effective at promoting early EBP. Students identified with the interactive, collaborative, and experiential nature of PBL to EBP instruction.

Metastatic myoepithelial carcinoma in a child.

Cutaneous myoepithelial tumors are rare entities, with few reported malignant variants in the literature. The majority of these tumors are reported in the head and neck region of the adult population, with few examples in the literature arising in young patients. We present a case of myoepithelial carcinoma in a 13-year-old girl, with documented metastatic disease. Reproducible predictors of malignant behavior have yet to be clarified.

Nevi with site-related atypia: a review of melanocytic nevi with atypical histologic features based on anatomic site.

A subset of melanocytic nevi share features with melanoma and nevi with architectural disorder but are biologically inert and to date do not appear to portend an increased risk for the development of malignancy. These benign nevi with certain atypical histologic features cluster among specific anatomic sites and are thus designated nevi with site-related atypia. We categorize these lesions into four main groups: acral, genital, special site and conjunctival, based on anatomy and relative prevalence of specific atypical histologic features. As the literature and our recognition of these lesions continue to grow, our understanding of their biology has not kept pace.

Acral myxoinflammatory fibroblastic sarcoma: case series and immunohistochemical analysis.

BACKGROUND: Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low-grade neoplasm most often occurring on the extremities of adults. It consists of mixed inflammatory infiltrates with nodules of epithelioid, spindled and bizarre-appearing cells within a fibrosclerotic-to-myxoid stroma. AMFS frequently recurs, but only rarely metastasizes. MATERIALS AND METHODS: A retrospective analysis of all cases of AMFS seen in the past 4 years from the Stanford University Laboratory of Surgical Pathology and collaborating institutions was performed. We sought to better characterize the clinicopathologic characteristics of this rare tumor. Immunohistochemical stains, including CD34, epithelial membrane antigen (EMA), epidermal growth factor receptor (EGFR), CD117, CD163, Ki67 and p53, were also performed. RESULTS: Eighteen cases were analyzed, and clinical information was available on 13 of them. The mean age at diagnosis was 48 years old, 10/13 (77%) occurred on the distal extremities and diameter of the lesions ranged from 1.0 to 10.0 cm. Treatment included wide local or radical excision and local recurrences were not reported. Many of the lesions were multinodular. Histologic characteristics included the presence of fibrosclerotic and myxoid stroma, sheets of spindled to round epithelioid cells, Reed-Sternberg or virocyte-like cells, lipoblast-like cells and rare mitotic figures. In most cases, CD34, EGFR and CD163 were diffusely positive. EMA and CD117 were weakly positive in some cases. Ki67 labeled < 10% of cells, and staining with P53 was variable. CONCLUSIONS: Because AMFS may be mistaken for lymphoma, infection or tumors with higher metastatic potential, correct diagnosis is important to avoid unnecessary procedures and allow for proper clinical management. EGFR positivity suggests possible therapeutic use in aggressive cases.

Dermatofibrosarcoma protuberans and giant cell fibroblastoma exhibit CD99 positivity.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

Brooke-Spiegler syndrome: report of a case of multiple cylindromas and trichoepitheliomas.

We report a case of Brooke-Spiegler syndrome, a rare autosomal dominant disorder caused by mutations of the cylindromatosis gene (CYLD) tumor suppressor gene resulting in multiple cylindromas and trichoepitheliomas. Treatment of these patients can involve surgical excision, laser therapy, or topical applications of aspirin derivatives.

Lymph node biopsy results for desmoplastic malignant melanoma.

Desmoplastic malignant melanoma (DMM) is a rare variant of melanoma with distinct histopathologic and clinical features. Compared with other melanomas, the desmoplastic variant demonstrates a greater frequency of local recurrence and a proclivity for tracking along nerves, but it poses a lower risk of distant metastases. Elective lymph node dissection and sentinel lymph node biopsy (SLNB) are commonly used tools for determining prognosis in thick melanomas. The role of these procedures for DMM remains unclear. This study was designed to characterize DMM and determine the frequency of histologically positive lymph nodes in patients with DMM. This retrospective chart review included patients with DMM treated by Johns Hopkins Hospital (JHH) physicians between 1998 and 2003. Among the 28 patients included in the study, 18 patients had biopsies performed on lymph nodes (15 SLNBs and 3 radical neck dissections). One patient had a sentinel lymph node with histology positive for DMM. All others had negative results from histology and S100 stains. This study suggests that the frequency of positive SLNBs in DMM may be substantially lower than that of other melanomas.

Identification and optimization of anthranilic sulfonamides as novel, selective cholecystokinin-2 receptor antagonists.

A high throughput screening approach to the identification of selective cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4-ylsulfonyl)amino]-5-chlorobenzoyl]-piperidine (1; CCK-2R, pK(I) = 6.4). Preliminary exploration of the structure-activity relationships around the anthranilic ring and the amide and sulfonamide moieties led to a nearly 50-fold improvement of receptor affinity and showed a greater than 1000-fold selectivity over the related cholecystokinin-1 receptor. Pharmacokinetic evaluation led to the identification of 4-[4-iodo-2-[(5-quinoxalinylsulfonyl)amino]benzoyl]-morpholine, 26d, a compound that demonstrates promising pharmacokinetic properties in the rat and dog with respect to plasma clearance and oral bioavailability and is a potent inhibitor in vivo of pentagastrin-stimulated acid secretion in the rat when dosed orally.

Standing on the Precipice: Evaluating Final-Year Physiotherapy Students' Perspectives of Their Curriculum as Preparation for Primary Health Care Practice.

Purpose: To explore final-year physiotherapy students' perceptions of primary health care practice to determine (1) aspects of their curriculum that support their learning, (2) deficiencies in their curriculum, and (3) areas that they believe should be changed to adequately equip them to make the transition from student to primary health care professional. Methods: Framework analysis methodology was used to analyze group opinion obtained using structured group feedback sessions. Sixty-eight final-year physiotherapy students from the four higher education institutions in Ireland participated. Results: The students identified several key areas that (1) supported their learning (exposure to evidence-based practice, opportunities to practise with problem-based learning, and interdisciplinary learning experiences); (2) were deficient (primary health care placements, additional active learning sessions, and further education and practice opportunities for communication and health promotion), and (3) required change (practice placements in primary health care, better curriculum organization to accommodate primary health care throughout the programme with the suggestion of a specific primary health care module). Conclusion: This study provides important insights into physiotherapy students' perceptions of primary health care. It also provides important indicators of the curriculum changes needed to increase graduates' confidence in their ability to take up employment in primary health care.

Objectif : Explorer les perceptions qu'ont les étudiants de dernière année en physiothérapie des soins primaires afin de déterminer (1) les aspects du curriculum qui favorisent leur apprentissage, (2) les lacunes dans le curriculum et (3) les changements nécessaires pour mieux les préparer à la profession en soins primaires. Méthodes : Les opinions du groupe ont été recueillies lors de séances de groupe structurées et analysées au moyen d'un cadre méthodologique analytique. Soixante-huit étudiants de dernière année en physiothérapie des quatre établissements d'enseignement supérieur d'Irlande ont pris part à l'étude. Résultats : Les étudiants ont relevé des (1) éléments favorables à leur apprentissage (exposition à la pratique fondée sur les données probantes, apprentissage par problèmes, expériences d'apprentissage interdisciplinaire); (2) des lacunes (manque de stages en soins primaires, de séances d'apprentissage actif et de formation en communication et en promotion de la santé); (3) et des changements nécessaires (stages en soins primaires, réorganisation du curriculum afin d'intégrer les soins primaires tout au long du programme, inclusion d'un module spécifique sur les soins primaires). Conclusion : Cette étude apporte un éclairage utile sur les perceptions qu'ont les étudiants en physiothérapie des soins primaires. Elle met également au jour les changements qui s'imposent afin d'améliorer la confiance des diplômés en leur capacité de pratiquer en soins primaires.

Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.

The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues. USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C) targets USP22 for degradation by using the substrate adapter CDC20 during cell exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size. Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression.

Disseminated cellulitic cryptococcosis in the setting of prednisone monotherapy for pemphigus vulgaris.

Cryptococcal infections are seen mainly in immunocompromised hosts. The cutaneous manifestations of infection can include papules, plaques, nodules, vesicles, ulcers, ecchymosis, and, rarely, cellulitis. Cryptococcal meningitis is a life-threatening complication of this disease. Pemphigus vulgaris is a rare auto-immune blistering disease that can also be life-threatening. Treatment of pemphigus commonly entails both corticosteroids and steroid-sparing agents. We present a case of disseminated cryptococcal infection in a patient with pemphigus vulgaris treated with high dose corticosteroids as monotherapy. This case provides an opportunity to discuss the difficulty of managing two potentially mortal conditions in which the treatment of pemphigus vulgaris may exacerbate the disseminated cryptococcal infection.

Art interpretation as a clinical intervention toward healing.

Art interpretation is described as a clinical approach in assisting individuals to move toward ever higher levels of wellness. Using it with healthy as well as ill individuals prompts participants to attend to the connection between themselves and the larger world. Asking individuals in a group setting to look closely at art, to make a connection between what they see and their own life experiences, can help them give voice to emotional experiences that help them connect to one another within a community. The exercise can sharpen perceptual and cognitive skills as well as provide the impetus to increase communication. Very often, participants responded to conversational prompts with new insights that were mediated through the use of the observed works of art. Making such connections, mentally, spiritually, emotionally, and socially, is helpful in developing coping skills that teach such patients new ways to not only survive but also to thrive despite their health challenges.

Measurement of walking activity throughout childhood: influence of leg length.

The aim of this study was to describe walking (stride) activity frequency and intensity in 428 children ages 2-15 years with a single accelerometer-based device. With comparison with published pedometer-determined data, the influence of leg length was examined. Decline in stride frequency and intensity throughout childhood increased with adjustment for leg length. The accelerometer-based device documented higher stride counts than published pedometer-based data with the greatest discrepancy in 4-5 year olds. Recommended walking levels for optimal weight throughout childhood should be examined with knowledge of the device measurement differences and the natural history of walking activity changes with age.